Pancreatic cancer accounts for 30,500 new cases annually, with a dismal 5-year survival rate of 15% when respectable, down to 1.8% when distant metastases are present. Approximately 80-95% of cases are unresectable at diagnosis, leading to the poor survival outcomes. Currently, gemcitabine as a single agent is considered the first line therapy for pancreatic cancer. Multiple "doublets" have been studied in phase III trials, pairing gemcitabine with pemetrexed, oxaliplatin, 5-FU, irinotecan and cisplatin, but none have proved superior in overall survival to gemcitabine alone. Oxaliplatin paired with gemcitabine had the most promise, with improved progression-free survival (2 months), and is currently being used (Louvet, JClin Onc 2005(23) p.3509) . One triplet that has been studied in metastatic disease, gemcitabine, capecitabine and docetaxel, showed promising outcomes. After 9 cycles, the results were: 11% complete response (CR), 39% partial response (PR), and 24% stable disease. One year survival was 43%, 2 year was 17% (Fine, Proc ASCO 2003, Abstract 1129 and Fogelman, Proc ASCO 2003, Abstract 1517). Erlotinib has recently been approved in combination with gemcitabine due to its improved 1 year survival (24% vs. 17% with placebo p=0.025) and progression-free survival (32% vs. 25%, p=0.003) (Moore, Proc ASCO 2005, Abstract 1). Phase III studies are ongoing utilizing cetuximab, bevacizumab, oxaliplatin, capecitabine, and vaccine therapies. Erlotinib is the first therapy approved for pancreatic cancer since gemcitabine, which has created a lot of excitement in the pancreatic cancer community. Perhaps pairing these drugs with other novel agents will provide even more hope for these patients.